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Epidemiology Exam II Material > Lecture #16-19 Interventional Studies > Flashcards

Lecture #16-19 Interventional Studies Flashcards

1
Q

What are other terms used to explain interventional study designs

A

Clinical trial, clinical study, experimental study, human study, investigational study

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2
Q

What is the key difference between observational and interventional studies

A

Investigator selects “interventions” and allocates study subjects to forced-intervention groups in interventional studies

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3
Q

Which type of study observational or interventional is able to demonstrate causation

A

Interventional. It is more “rigorous” in ability to show a cause- and-effect

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4
Q

What does Pre-Clinical mean

A

It is a phase of interventional studies.
of all the phases it has the lowest strength of evidence
it is prior to human investigation
bench and animal research

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5
Q

what is phase 1

A 
It is a phase of interventional studies
it is after the pre-clinical phase
small N (about 20-80), healthy volunteers (can also be sick) are  used for the first time in humans to assess safety/toxicity, dosing and even pharmacokinetics in population of interest (diseased)
- short duration (e.g. usually just a few days or weeks or couple of months)
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6
Q

How long does phase 1 of interventional studies last

A

short duration

usually a few days or weeks or couple of months

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7
Q

What is the typical sample size for phase 1 of interventional studies

A

small about 20-80

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8
Q

Explain phase 2 trials

A 
larger N (about 100-300 people) commonly utilize patients with condition of interest, used to expand on purpose of Phase 1 study (safety) but also to begin assessing efficacy in diseased population
short-to-medium duration (few to several months)
Likely to have a narrower inclusion criteria
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9
Q

What is the sample size in phase 2 trials

A

about 100-300 patients

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10
Q

What is the duration of Phase 2 trials

A

shot to medium duration (a few to several months)

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11
Q

who is the typical study sample for phase 2 trials

A

about 100-300 patients,

commonly utilize patients with condition of interest

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12
Q

what is the purpose of phase 2 trials

A

used to expand on purpose of phase 1 study (safety) but also to begin assessing efficacy in diseased population

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13
Q

who is used in phase 1 trials

A

healthy volunteers (can use sick volunteers, this is usually done in cancer research)

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14
Q

What is the purpose of phase 1 trials

A

to assess safety/toxicity, dosing and even pharmacokinetics in population of interest (diseased)

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15
Q

Explain a Phase 3 trial

A

after phase 2
larger N (about 1,000-3,000) used in patients with condition of interest to continue determination of safety, with primary purpose to assess efficacy
- Longer duration (many months to a year (or few years)
- Superiority vs. Non-Inferiority vs. equivalency formats

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16
Q

what is the sample size for phase 3 trials

A

about 1,000-3,000 patients with conditions of interest

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17
Q

What is the purpose of phase 3 trials

A

To continue determination of safety, with primary purpose to assess efficacy

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18
Q

What is the duration of a phase 3 trial

A

many months to a year (or a few years)

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19
Q

What kind of patients are used for phase 3 trials

A

Patients with the condition of interest

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20
Q

what is a phase 4 study

A

Post-marketing
Long -term effects (risk and benefits) in a large population of diseased patients (expanded use population (age, ethnic))

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21
Q

Phase 4 studies utilize what

A

Registries, Surveys’s (ex. FDA’s MedWatch/FAERS/VAERS programs)

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22
Q

what is the purpose of a phase 4 study

A

Long-term effects (risk and benefits) in a large population of diseased patients

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23
Q

who is used in phase 4 studies

A

large population of diseased patients

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24
Q

What are some advantages of interventional trials vs. other designs

A

Cause precedes effect (shows causation)

only design used by FDA for “approval” process (on-label)

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25
Q

What are some disadvantages of interventional trials vs. other designs

A

Cost, Complexity/time (development/approval/conductance)
Ethical considerations (risk vs. benefit evaluation)
Generalizability (a.k.a External Validity)

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26
Q

What are 4 types of designs of interventional studies

A

Simple, Factorial,Parallel, Cross-over (a.k.a. Self-control)

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27
Q

Explain a simple interventional study

A

Divides (randomizes) subjects exclusively into greater than or equal to 2 groups
- a single randomization process; no subsequent randomized divisions
Commonly used to test a single hypothesis (question) at a time.

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28
Q

When is a simple interventional study commonly used

A

to test a single hypothesis (question) at a time

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29
Q

How many groups does a simple interventional study divide (randomize) subjects into

A

Greater than or equal to 2 groups

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30
Q

Explain a factorial interventional study

A

Divides subjects into greater than or equal to 2 groups and then further additionally sub-divides (randomizes) each of the groups into greater than or equal to 2 sub-groups

- numerical representation of numbers of groups and number of divisions ( 2x2 or 3x3x2) * * used to test multiple hypotheses at the same time (increases sample size requirement)
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31
Q

Why is a factorial interventional study design used

A

to test multiple hypotheses at the same time (increases sample size requirement)

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32
Q

what some characteristics of factorial interventional study designs

A

improves efficiency for answering clinical questions
increases study population sample size (due to increased group #)
increases complexity (which may be a barrier to recruitment)
Increases risk of drop outs (due to complexity)
may restrict generalizablility of results

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33
Q

What are some weaknesses of factorial interventional study designs

A

increases study population sample size (due to increased group #)
increases complexity (which may be a barrier to recruitment)
Increases risk of drop outs (due to complexity)
may restrict generalizablility of results

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34
Q

What are some strengths of factorial interventional study designs

A

Improves efficiency for answering clinical questions, used to test multiple hypotheses at the same time

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35
Q

Explain Parallel interventional study designs

A

Groups simultaneously and exclusively managed
No switching of intervention groups after initial randomization
- all simple and factorial study designs are also parallel

36
Q

All simple and factorial study designs are also what

A

Parallel study designs

37
Q

Explain Cross-Over (aka Self-Control)

A

Groups serve as their own control by crossing over form one intervention to another during the study

 - allow for a smaller total "N" (sample size) 
            - each patient contributes additional data
38
Q

What is the Run-In/ Lead-In phase

A

a way to assess placebo-effects, Hawthorne-effects and compliance BEFORE a study begins

  • all study subjects blindly given one or more placebos for initial therapy (defined time-period) to determine a “new” base-line of disease (standardization)
    • can assess study protocol compliance
    • Can “ wash-out” existing medications
      - Reduces at least 1 possible common exclusion criteria
      • can determine amount of placebo-effect (new baseline
39
Q

what are 6 disadvantages of Cross-Over interventional study designs

A
  • only suitable for long-term conditions which are not curable or which treatment provides short-term relief
  • duration of study for each subject is longer
  • carry-over effects during cross-over (wash-out required; which prolongs study duration)
  • Treatment-by-Period interaction
    - Differences in effects of treatments during different time periods
  • Smaller N requirement only applicable if within-subjects variation less than between-subjects variation
  • complexity in data analysis
40
Q

What are the phases of interventional study designs that are largely concerned with safety.

A

Phase 1 and 4

41
Q

Which phases of interventional study design are mostly concerned with efficacy and effectiveness

A

Phase 2 and 3

42
Q

Will you ever see a drug without a name in a phase 4 trial

A

No!

43
Q

Is safety a concern in all phases of a study

A

Yes but may not be the main focus in phases 2 and 3

44
Q

Dummy in terms of epidemiology means what

A

placebo

45
Q

Equipoise

A

Genuine confidence that an intervention may be worthwhile (risk vs. Benefit) in order to use it in humans

46
Q

What are some advantages of interventional trials vs. other designs

A

cause precedes effect (shows causation)

only design used by FDA for “approval” process (on-label)

47
Q

what are some disadvantages of interventional trials vs. other designs

A
  • Cost
  • complexity/Time (development/approval/conductance) because they are prospective in nature
  • Ethical considerations (risk vs. benefit evaluation)
  • Generalizability (a.k.a; External validity)
48
Q

What is usually the number one reason why observational studies are better

A

Ethics

49
Q

What is the difference between explanatory and pragmatic studies

A

explanatory has a rule to play by and can’t manipulate it per patient
pragmatic trials allow you to use clinical practices to manipulate the studies
pragmatic trials never really use placebos
Pragmatic let regular people in

50
Q

What does it mean that pragmatic trials let regular people in

A

The allow people with multiple comorbidities and on multiple medications

51
Q

What is a weakness of pragmatic studies

A

loss of control and may have multiple cofounders present

52
Q

The fluid mosaic model describe the overal organization of a biological membranes. The essence of their model is that memrbanes are _______ dimensional solutions of______ and ______

A

Two, oriented lipids, globular proteins

53
Q

what is the lipid bilayers dual roles

A

it is a solvent for integral membrane proteins and a permeability barrier

54
Q

what does within group and between group during cross-over study mean

A

Between groups is the normal comparision between A and B. In group refers to the ability to see how an individual performs when they are in both groups (self-control)

55
Q

What are the disadvantages of Cross-Over design

A
  • only suitable for long-term conditions which are not curable or which treatment provides short-term relief
  • Duration of effects during cross-over (wash-out required; which prolongs study duration)
  • Treatment-by-Period interaction
    • Differences in effects of treatments during different time periods
  • Smaller N requirement only applicable if within subjects variation less than between subjects variation
  • complexity in data analysis
56
Q

Examples of Patient-Oriented Endpoints (most clinically relevant)

A

Death, Stroke or MI, Hospitalization, preventing need for dialysis

57
Q

Examples of surrogate Markers (elements used in place of evaluating patient-oriented (direct) endpoints

A

Blood pressure (for risk of stroke), Cholesterol (for risk of heart attack), Change in SCr (for worsening renal function)

58
Q

What are convenience sampling/non-probabilistic allocation

A

Non-random sampling

59
Q

What is the major purpose of Randomization

A

To remove bias and make groups as equal as possibel

60
Q

is equality of groups guaranteed when using randomization

A

No

61
Q

What is Table 1

A

It shows you how the randomization shook out and the statistics to show the groups equality

62
Q

_______ attempts to reduce systematic differences (bias) between groups which could impact results/outcomes

A

Randomization

63
Q

What are 3 examples of forms of randomization

A

simple, blocked, stratified

64
Q

What is simple randomization

A

equal probability for allocation within one of the study groups

65
Q

What is blocked randomization

A

ensures balance within each intervention group

- used when researcher wants all groups to have equal size

66
Q

What is stratified randomization

A

ensures balance with known confounding variables
- examples: gender, age, disease severity/ duration, comorbidites
can also pre-select levels to be balanced within each interfering factor (confounder)

67
Q

What are three kinds of masking

A

single-blind, doube-blind, open-label

68
Q

What is a single-blind study

A

Study subjects are not informed which intervention they are receiving (but clinicians/researchers are)

69
Q

What is a double blind study

A

Neither investigators nor study subjects are informed which intervention each subjects is receiving

70
Q

What is a open-label study

A

Everyone knows which intervention each subject is receiving

71
Q

What is a post-hoc’s survey

A

can be used to assess adequacy of blinding

72
Q

When is a single-blind okay

A

When the researcher is not interacting with them and is unable to influence the results

73
Q

What is a placebo (dummy) therapy

A

inert treatments made to look identical in all aspects to the active treatments
- dosage forms, dosing frequency, monitoring, therapy requirements, etc.

74
Q

What is a double-dummy

A

more than 1 placebo used

75
Q

What is the placebo effect

A

Improvement in condition; by power of suggestion and due to the care being provided
- can be as large as 30-50%

76
Q

Hawthorne-effect

A

Desire of study subject to “please” investigators by reporting positive results (improvement), regardless of treatment allocation.
- desire for positive outcome to process

77
Q

How large can the placebo effect be

A

30-50%

78
Q

Post-hoc sub-group analysis is _______ as appropriate, by most, when not prospectively planned

A

Not accepted

79
Q

What is post-hoc sub-group analysis called when it is retrospective

A

Data-dredging or fishing

80
Q

Post-hoc sub-group analysis can do what the the power and increases the risk of what

A

Reduces power and increases risk of Type 2 error

81
Q

In sample size determination they add in who

A

anticipated drop-out or loss to follow up rates

82
Q

How can one manage drop-outs/Lost-to-follow-ups

A

Intent-to-treat and Per-protocol or Efficacy-Analysis, as-treated

83
Q

What is the most conservative decision on how to manage drop-outs/lost-to-follow ups

A

Intent-to-Treat

84
Q

Explain Intent-to-Treat

A

The most conservative way to manage drop-outs/lost-to-follow up
- last known assessment (observation) used for (carried forward) all subsequent, yet missed assessment (LOCF)
- Convert all subsequent yet missed assessments for a subjects to a null-effect (no-benefit)
-preserves randomization process
- Preserves baseline characteristics and group balance at
baseline which controls for known and unknown confounds
- Maintains statistical power (original sample size)

85
Q

What is per-protocol or efficacy-analysis

A

compliance must be pre-defined

- customarily set at 80-90 % with study protocol

86
Q

Wash-Out period

A

The longest period needed to reduce both groups to baseline

87
Q

The post hoc analysis must be

A

Pre-defined and compliance must be greater than 80-90%

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